The object of this study is to examine the prospect that an important mode of action of the amphetamines is by modulation of the activity and turnover of the catecholamine synthesizing enzymes, tyrosine hydroxylase, pteridine reductase, dopa decarboxylase and dopamine-beta-hydroxylase. To accomplish this we first plan to purify the enzymes, characterize their properties including the presence of multiple forms, produce specific antibodies to each enzyme, measure the amounts of enzyme regionally in brain by immunoprecipitation and radioimmunoassay, and determine the localization immunohistochmically. Then we shall examine the action of amphetamine and metabolites in vitro on the kinetics of the purified enzyme. Finally, we shall study the action of acute and chronic administration of amphetamine on the amounts and rates of synthesis and degradation of the enzymes regionally in brain. Bibliographic references: Joh, T.H. and Reis, D.J.: Different forms of tyrosine hydroxylase in central dopaminergic and noradrenergic neurons and sympathetic ganglia. Brain Res. 85: 146-151, 1975; Reis, D.J. Joh, T.H. and Ross, R.A.: Effects of reserpine on activities and amounts of tyrosine hydroxylase and dopamine-beta-hydroxylase in catecholamine neuronal systems in rat brain. J. Pharmacol. Exp. Ther. 193: 775-784, 1975.